Knowledge of clinicians/pediatricians about neonatal resuscitation in a tertiary care hospital.

OBJECTIVE: To analyze the knowledge of the doctors dealing with pediatric patients about neonatal resuscitation. METHODS: This was a cross sectional study conducted at The Lahore General Hospital over one year. Total 137 doctors related to pediatrics with different job descriptions were enrolled and requested to fill a questionnaire proforma regarding their knowledge about basic equipment required and about neonatal resuscitation steps. Data was entered and analyzed using SPSS 20. RESULTS: Out of 137 participants, majority (71%) had >2 years of experience in pediatrics and 52.5% had higher postgraduate qualification. Neonatal resuscitation workshop was attended by 57% doctors. In resuscitation of newborns at the time of delivery, resuscitating doctors were assisted by nurse in 50%, by junior doctor in 35%, paramedic staff 11% and it was done by single doctor in 4% cases. Oxygen (central or O2 cylinder) and warmer facilities were available in 90% and 82% of health facilities respectively. Majority (86%) of participants were of view that every neonate must be attended at birth. Not a single doctor followed all the standard steps of neonatal resuscitation although 90% had knowledge about resuscitation equipment and common resuscitation drugs. CONCLUSION: Pediatric health care professionals had knowledge about neonatal resuscitation but there are gaps in the practical application. There is a strong need of frequent neonatal resuscitation workshops for improving neonatal outcomes.

Is human milk feeding protective for Retinopathy of Prematurity?

OBJECTIVE: To find the association between breast milk feeding with retinopathy of prematurity (ROP) in preterm infants. METHODS: This was a cross sectional study to examine the effects of breast milk feeding on ROP. Premature newborns below 34 weeks from neonatal unit retinopathy of prematurity program during the years 2015 to 2017 of The Lahore General Hospital were included. We recorded the gestational age, birth weight, presence of ROP and the type of feeding (breastfeeding vs. formula milk). RESULTS: Out of 428 preterm babies 210 (49%) were males. More babies were between 32-34 weeks of gestation 229 (53.5%) as compared to < 32 weeks 199 (46.5%). Among all 428 preterm infants 19(4.4%) developed ROP. Majority 13 (68.4%) who developed ROP were <32 weeks of gestation (p=0.042). The mean birth weight of infants without ROP was 1.51± 0.36 kg (95%CI; 1.47-1.55), while it was 1.36 ± 0.29 kg (95%CI; 1.22-1.50) with ROP and all who developed ROP were < 2kg. The estimated odds ratio of developing ROP for breast fed versus top feeding was (ORs: 0.571, 95% CI; 0.222- 1.489). There was a trend toward lower incidence of ROP in the group of newborns who received breast-feeding (36.8%) as compared to top feeding (63.2%) but almost similar percentage who didn't develop ROP were breast fed or top fed with statistically insignificant results (p= 0.24). CONCLUSIONS: Slightly lesser percentage of preterm babies who were breast fed developed retinopathy of prematurity.

Paraneoplastic Cushing Syndrome Due To Wilm's Tumor.

Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to neoplasm. Paraneoplastic syndromes may be the first or the most prominent manifestations of cancer. Wilm's tumor is the most frequent pediatric renal malignancy and usually presents with abdominal mass. Unusual presentations like acquired von Willebrand disease, sudden death due to pulmonary embolism and Cushing syndrome have been described in the literature. Cushing syndrome, as the presenting symptom of a malignant renal tumor in children, is a very rare entity. Few case reports are available in the literature exploring the option of preoperative chemotherapy as well as upfront nephrectomy. We report a rare case of paraneoplastic Cushing syndrome due to a Wilm's tumor. Based on gradual decrease of postoperative weight, blood pressure, serum adrenocorticotropic hormone, and plasma cortisol levels, along with histological confirmation of Wilm's tumor, paraneoplastic Cushing syndrome due to Wilm's tumor was confirmed.

Comparison of Presentation and Outcome in 100 Pediatric Hodgkin Lymphoma Patients Treated at Children Hospital, Lahore, Pakistan and Royal Marsden Hospital, UK.

OBJECTIVE: To compare differences in demographics and outcomes in childhood Hodgkin lymphoma (HL) presenting at the Children's Hospital Lahore (CHL), and Royal Marsden Hospital (RMH), UK. STUDY DESIGN: An observational comparative study. PLACE AND DURATION OF STUDY: From January 2011 to February 2012 at CH, Lahore and from October 2008 to February 2012 at RMH, UK. METHODOLOGY: Consecutive HL patients (50 from each hospital) were inducted. Data regarding age, gender, staging, histopathology and outcome were analysed. Clinical and pathological staging done according to Ann-Arbor and World Health Organization classification. Treatment duration was 6-8 months. They were followed for 6 months post-treatment. Frequencies of variables were noted and compared. Chi-square test was used for determining significance. RESULTS: Patients from Children's Hospital, Lahore were younger (mean 7.9 years) with male predominance (n=42, 84%). Histopathology showed Mixed Cellularity (MC) in 32 (64%), Nodular Sclerosis (NS) in 5 (10%), Lymphocyte Rich in 4 (8%) and lymphocyte depleted in 1 (2%), nodular lymphocyte predominant (NLP) in 1 (2%) each. Majority presented in stage IV (n=25,50%), or stage III (n=20,40%). Constitutional B symptoms were present in 37 (74%). Bone marrow involvement observed in 23 (46%). Remission was achieved in 42 (84%) patients; 2 (4%) relapsed, 4 (8%) expired and 2 (4%) left against medical advice. In contrast, RMH patients were older (mean 11.8 years.) and 30 (60%) were males. NS (n=40,80%) and NLP (n=6,12%) types were predominant. Two (4%) patients were in stage I, 27 (54%) in stage II, 12 (24%) in stage III and 9 (18%) presented in stage IV. Fourteen (28%) had B-symptoms. None had bone marrow disease. Event free survival was 46 (92%). Four (8%) patients relapsed. Three responded to second line therapy and one relapsed postautologous transplant. CONCLUSION: Significant differences were observed in age at presentation, stage, histopathology and extent of bone marrow involvement between the groups. Of interest is the bone marrow involvement in stage IV patients in Pakistan. Delayed diagnosis account for advanced stage but difference in pathological subtype needs further study.

Ollier's Disease with Myelodysplastic Syndrome.

Ollier's disease also known as enchondromatosis is a rare skeletal disorder that is usually sporadic, non-hereditary, and characterized by abnormal bone development (skeletal dysplasia). While this disorder may be present at birth (congenital); it may not become apparent until early childhood with more obvious symptoms, such as deformities or improper limb growth. It carries high risk of skeletal, visceral and brain malignancy seen in approximately 25% of patients. Occurrence of Ollier's disease with myelodysplastic syndrome has never been reported in the literature. The different types of myelodysplastic syndromes are diagnosed based on certain changes in the blood cells and bone marrow characterized by one or more cytopenias despite a relatively hypercellular bone marrow. We hereby report the case of a 14 years boy who presented with painless finger swelling and hepatosplenomegaly. Radiological and bone marrow findings confirmed the diagnosis of Ollier's disease with Refractory Anemia and Excess Blasts (RAEB-1).

Intrarenal neuroblastoma: a diagnostic challenge.

Abdominal masses in children are usually retroperitoneal in location and 50% are renal in origin. In infants less than 2 months, majority of renal masses are benign; frequency of malignancy increases with age. Wilms'tumor is the commonest solid intrarenal tumors. However, occasionally neuroblastoma occurs in the kidney. Neuroblastoma in 50% of cases presents before 2 years of age, and 75% before 4 years. Neuroblastomas can occur anywhere along the neuroectodermal sympathetic chain, although adrenal medulla is the commonest site (50 - 70%). Intrarenal neuroblastoma is a rare clinical diagnosis. It clinically and radiologically mimics Wilms'tumor and it is difficult to differentiate between the two preoperatively. Lung metastasis and vascular invasion are also rare in neuroblastoma but rather common in Wilms'tumor. We present case of a patient who had extensive renal involvement with neuroblastoma and pulmonary metastasis, clinically and radiologically it was difficult to differentiate between the Wilms'tumor and neuroblastoma.

Primary renal Ewing's sarcoma: a rare entity.

Ewing's sarcoma, a primitive neuroectodermal tumour is a rare entity belonging to a family of neoplasms of neuroectodermal origin. These highly aggressive neoplasms primarily affect older children and young adults. They primarily involve the bones or soft tissues. A quarter of Ewing's sarcomas occur principally in the soft tissues with primary involvement of the kidney being exceptionally rare. We hereby, present a case of 6 years old girl child with primary Ewing's sarcoma of the kidney who presented with abdominal mass and posed much diagnostic challenge. The patient underwent complete surgical excision of tumour, and is being treated with aggressive adjuvant chemotherapy.

Prognostically significant fusion oncogenes in Pakistani patients with adult acute lymphoblastic leukemia and their association with disease biology and outcome.

BACKGROUND AND OBJECTIVES: Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome. METHODS: We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome. RESULTS: Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL positive patients had frequent organomegaly and usually presented with a platelets count of less than 50 x10(9)/l. Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome. CONCLUSIONS: This is the first study from Pakistan which investigated the frequency of 5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome. Frequencies of some of the oncogenes were different from those reported elsewhere and they appear to be associated with distinct clinical characteristics and treatment outcome. This information will help in the prognostic stratification and risk adapted management of adult ALL patients.

Five most common prognostically important fusion oncogenes are detected in the majority of Pakistani pediatric acute lymphoblastic leukemia patients and are strongly associated with disease biology and treatment outcome.

BACKGROUND AND OBJECTIVES: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome. METHOD: We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome. RESULTS: Five most common fusion genes i.e. BCR-ABL t (22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 89/101 (88.1%) patients. Frequency of BCR-ABL was 44.5% (45/101). BCR-ABL positive patients had a significantly lower survival (43.7±4.24 weeks) and higher white cell count as compared to others, except patients with MLL-AF4. The highest relapse-free survival was documented with ETV6-RUNX1 (14.2 months) followed closely by those cases in which no gene was detected (13.100). RFS with BCR-ABL, MLL-AF4, TCF3-PBX1 and SIL-TAL1 was less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively). CONCLUSIONS: This is the first study from Pakistan correlating molecular markers with disease biology and treatment outcome in pediatric ALL. It revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, associated with poor overall survival. Our data indicate an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.

The effect of consecutive extended duty hours on the cognitive and behavioural performance of paediatric medicine residents.

OBJECTIVES: To compare the performance of paediatric medicine residents following a regular 6 hour and an extended 24 hour call and their own insight into their performance following each duty. METHOD: The study was conducted at The Children's Hospital, Lahore, from September 2007 to November, 2008. All tasks were performed twice, after 6 hour call and 24 hour long call, evaluating Reaction timer, Concentration test, Number Connection Test, State Trait Anger Anxiety Inventory (STAXI) response for trait anger and modified Wechsler Memory Scale inventory (WMS-R) for cognitive performance. Likert's self assessment tool was used for both set of performances. RESULT: Thirty two paediatric medicine residents (male 53.1%; female 46.9%) were enrolled in the study with identical duty structure performing 74 hours per week with mean age of 27.53 +/- 0.32 years and mean experience of 3.69 +/- 0.32 years. There was significant deterioration in both verbal recall and logic memory (mean difference in score of 1.81 (95% C.I 1.25-2.37, p < 0.001). Concentration test also showed significantly fewer responses (24 hour mean 239.56, 95% C.I. 228-251.13) vs (6 hour mean 258.94, 95% C.I. 247.42-270.46) in 5 minutes, p < 0.001. Reaction time, vigilance and hand eye coordination was significantly affected after an extended call, p < 0.001. Number of lapses in attention also rose significantly, p < 0.001. STAXI response showed significant increase in anger scores, p = 0.001. Despite the significantly poor performance, the residents could not appreciate the deterioration in their performance with Likert's self assessment score that differed only by 0.63 (95% CI -0.12-1.37), p = 0.1. None of the other factors studied correlated with deterioration in performance of any specific task except the length of duty hours. CONCLUSION: Continuous long stretch of duty causes significant deterioration in cognitive and behavioural status of residents. More importantly, the residents themselves are unable to appreciate this deterioration. Residents must be made aware of this deterioration as there is a higher risk of medical errors and bad judgments, risking patient safety.

Disproportionate short stature with multisystem involvement - Ellis-van Creveld syndrome.

Ellis-van Creveld syndrome is a rare form of mesenchymal - ectodermal dysplasia. It is an autosomal recessive disorder characterized by disproportionate short stature, postaxial polydactyly, ectodermal dysplasia and congenital heart defect. This case report presents two cases with classical clinical findings along with some unusual features including rhizomelic limb shortening, global developmental delay and bilateral lens subluxation not reported previously.

Comparison of three prognostic scores (PRISM, PELOD and PIM 2) at pediatric intensive care unit under Pakistani circumstances.

BACKGROUND: To compare the performance of the Pediatric Risk of Mortality (PRISM), the Pediatric Index of Mortality 2 (PIM 2) and Pediatric Logistic Organ Dysfunction (PELOD) scores at general pediatric intensive care unit in a developing country setting, investigating the relation between observed and predicted mortality. METHOD: A contemporary cohort study was undertaken at Pediatric Intensive Care Unit (PICU), Children's Hospital, Institute of Child Health, Lahore, Pakistan. 131 consecutive admissions fulfilling the inclusion criteria were enrolled in the study. PRISM, PIM 2 and PELOD calculations were performed as set out by original articles, using the published formulae. Statistical analysis included Standardized Mortality Rate (SMR), Hosmer Lemeshow goodness of fit test, receiver operating curve (ROC) characteristics and Spearman's correlation test. RESULTS: 139 patients were admitted to PICU. 38 presented exclusion criteria. 29 (28.7%) patients died. Estimated mortality was; PRISM: 19.7(19.5%), PIM: 21.01(20.5%) and PELOD:18.4(18.3%). SMR was 1.47 (SD +/- 0.19), 1.4 (SD +/- 0.19) and 1.57 (SD +/- 0.19), respectively. PRISM had better calibration (x2 = 7.49, p = 0.49) followed by PIM 2 (x2 = 9.65, p = 0.29). PIM 2 showed best discrimination with area under ROC = 0.88 (0.81-0.94) followed by PRISM 0.78 (0.67-0.89) and PELOD 0.77 (0.68-0.87). Spearman's correlation r between PRISM and PIM 2 returned 0.74 (p < 0.001). CONCLUSION: PRISM as well as PIM 2 is validated for PICU setting in Pakistani circumstances. PELOD performed poorly. PIM 2 has advantages over PRISM for stratification of patients in clinical trials.

Enzyme replacement therapy in a child with Gaucher disease.

This case report describes an experience of using recombinant enzyme in a child who was diagnosed as a case of Gaucher disease at the age of 3 years. Regular enzyme replacement therapy has resulted in marked improvement in his hemoglobin level, absolute neutrophil count, platelets and physical growth.